This study (TiCAB) is designed as a pivotal efficacy and safety study of Ticagrelor in patients undergoing coronary artery bypass operation. It is designed for the prevention of fatal and non-fatal cardiovascular events in this patient population, a significant, yet unmet medical need.

Detailed Description

For stable patients who underwent coronary bypass operation, Aspirin alone currently represents the gold standard of antiplatelet treatment. A few smaller studies using a combination therapy of antiplatelet drugs including Aspirin and Clopidogrel have shown conflicting results. Albeit a number of cardiac surgeons prefer dual antiplatelet therapy with Aspirin and Clopidogrel, Aspirin monotherapy is currently the only guideline recommended therapy after CABG.

A sub-analysis of PLATO trial comprising more than 1200 ACS patients who were not considered to be appropriately suited for PCI and therefore subjected to CABG operation demonstrated an impressive reduction in mortality in those patients treated with Ticagrelor and Aspirin as compared to Clopidogrel and Aspirin. The labeling of Ticagrelor says that the drug should be paused 7 days prior to surgery. However, a further analysis of this substudy revealed that the largest benefit in the Ticagrelor + Aspirin group as compared to the Clopidogrel + Aspirin group was found in those who stopped study medication at about 48 - 72 hours prior to surgery. There have been pharmacological studies that showed that Ticagrelor may precondition the heart for the trauma of surgery via adenosine mediated effects. Thus, the enormous benefit in the Ticagrelor arm of the PLATO study may be secondary to a pleiotropic action. There was no indication of an accelerated bleeding risk in this study and pharmacological studies document that platelet function should be largely restored of a pause of 48 - 72 hours, such that this duration may allow the optimal preparation for CABG surgery.

Based on the unmet clinical need regarding optimal antiplatelet therapy after CABG, the results of the PLATO CABG substudy and the observation that Ticagrelor benefits increase with decreasing Aspirin doses, Ticagrelor monotherapy (2x 90mg/day) appears to offer the best balance of safety with anticipated improved efficacy over Aspirin alone. However, there are no data available to support this hypothesis.